Multiplexed Plasma Immune Mediator Signatures Can Differentiate Sepsis From NonInfective SIRS: American Surgical Association 2020 Annual Meeting Paper.

OBJECTIVES: Sepsis and sterile both release "danger signals' that induce the systemic inflammatory response syndrome (SIRS). So differentiating infection from SIRS can be challenging. Precision diagnostic assays could limit unnecessary antibiotic use, improving outcomes. METHODS: After surveying human leukocyte cytokine production responses to sterile damage-associated molecular patterns (DAMPs), bacterial pathogen-associated molecular patterns, and bacteria we created a multiplex assay for 31 cytokines. We then studied plasma from patients with bacteremia, septic shock, "severe sepsis," or trauma (ISS ≥15 with circulating DAMPs) as well as controls. Infections were adjudicated based on post-hospitalization review. Plasma was studied in infection and injury using univariate and multivariate means to determine how such multiplex assays could best distinguish infective from noninfective SIRS. RESULTS: Infected patients had high plasma interleukin (IL)-6, IL-1α, and triggering receptor expressed on myeloid cells-1 (TREM-1) compared to controls [false discovery rates (FDR) <0.01, <0.01, <0.0001]. Conversely, injury suppressed many mediators including MDC (FDR <0.0001), TREM-1 (FDR <0.001), IP-10 (FDR <0.01), MCP-3 (FDR <0.05), FLT3L (FDR <0.05), Tweak, (FDR <0.05), GRO-α (FDR <0.05), and ENA-78 (FDR <0.05). In univariate studies, analyte overlap between clinical groups prevented clinical relevance. Multivariate models discriminated injury and infection much better, with the 2-group random-forest model classifying 11/11 injury and 28/29 infection patients correctly in out-of-bag validation. CONCLUSIONS: Circulating cytokines in traumatic SIRS differ markedly from those in health or sepsis. Variability limits the accuracy of single-mediator assays but machine learning based on multiplexed plasma assays revealed distinct patterns in sepsis- and injury-related SIRS. Defining biomarker release patterns that distinguish specific SIRS populations might allow decreased antibiotic use in those clinical situations. Large prospective studies are needed to validate and operationalize this approach.

Obstetrical Trauma: Reducing the Burden of Trauma Transfer to Tertiary Care Centers.

BACKGROUND: In rural state trauma systems, management of the obstetrical trauma patient often defaults to transfer to level I trauma centers. We evaluate the necessity of transferring obstetrical trauma patients without severe maternal injury. MATERIALS AND METHODS: A retrospective 5-year review of obstetrical trauma patients admitted to a rural state-level I trauma center was conducted. Injury severity measures such as abdominal AIS, ISS, and GCS were correlated with outcomes. Furthermore, the impact of maternal and gestational age on uterine compromise, uterine irritability, and the need for cesarean section intervention are presented. RESULTS: Twenty-one percent of patients were transferred from outside facilities with a median age of 29 years, average ISS of 3.9 ± 5.6, GCS of 13.8 ± 3.6, and abdominal AIS of 1.6 ± .8. Outcomes included maternal fatality of 2%, fetal demise of 4%, 6% experienced premature rupture of membranes, 9% experienced fetal placental compromise, 15% had uterine contractions, 15% of cesarean deliveries, and fetal decelerations occurred in 4%. Predictors of fetal compromise are strongly associated with high maternal ISS and low GCS. DISCUSSION: The frequency of traumatic injury in this unique population of patients is fortunately limited. The best predictor for fetal demise and uterine irritability is maternal injury severity, measured by ISS and GCS. Therefore, without severe maternal trauma, obstetrical trauma patients with minor injuries can safely be managed at non-tertiary care facilities with obstetrical capabilities.

A novel broad specificity fucosidase capable of core α1-6 fucose release from N-glycans labeled with urea-linked fluorescent dyes.

Exoglycosidases are often used for detailed characterization of glycan structures. Bovine kidney α-fucosidase is commonly used to determine the presence of core α1-6 fucose on N-glycans, an important modification of glycoproteins. Recently, several studies have reported that removal of core α1-6-linked fucose from N-glycans labeled with the reactive N-hydroxysuccinimide carbamate fluorescent labels 6-aminoquinolyl-N-hydroxysuccinimidylcarbamate (AQC) and RapiFluor-MS is severely impeded. We report here the cloning, expression and biochemical characterization of an α-fucosidase from Omnitrophica bacterium (termed fucosidase O). We show that fucosidase O can efficiently remove α1-6- and α1-3-linked core fucose from N-glycans. Additionally, we demonstrate that fucosidase O is able to efficiently hydrolyze core α1-6-linked fucose from N-glycans labeled with any of the existing NHS-carbamate activated fluorescent dyes.